Glucagon-like peptide receptors as targets for CoViD

Int J Mol Sci. 2019 Sep 14;20(18):4569. doi: 10.3390/ijms20184569.

Liraglutide Inhibits Hepatitis C Virus Replication Through an AMP Activated Protein Kinase Dependent Mechanism

Mei-Yueh Lee 1 2, Wei-Chun Chen 3, Wei-Hao Hsu 4 5, Szu-Chia Chen 6 7 8, Jin-Ching Lee 9 10 11 12


Insulin resistance and diabetes are both associated with chronic hepatitis C virus (HCV) infection, and the glucagon-like peptide-1(GLP-1) receptor agonist, liraglutide, is a common therapy for diabetes. Our aim was to investigate whether liraglutide treatment can inhibit HCV replication. A cell culture-produced HCV infectious system was generated by transfection of in vitro-transcribed genomic JFH-1 ribonucleic acid (RNA) into Huh-7.5 cells. Total RNA samples were extracted to determine the efficiency of HCV replication. The Ava5 cells were treated with liraglutide and cell viability was calculated. A Western blot analysis of the protein expression was performed. The immunoreactive blot signals were also detected. Liraglutide activated GLP-1 receptors in the HCV infectious system, and inhibited subgenomic HCV RNA replication in the HuH-7.5 cells. The Western blot analysis revealed both HCV protein and replicon RNA were reduced after treatment with liraglutide in a dose-dependent manner. Liraglutide decreased the cell viability of HCV RNA at an optimum concentration of 120 μg/mL, activated the 5′ adenosine monophosphate-activated protein kinase (AMPK) and the phosphorylated- transducer of regulated cyclic adenosine monophosphate (CAMP) response element-binding protein 2 (TORC2), thereby decreasing the cell viability of phosphoenolpyruvate carboxykinase (PEPCK) and G6pase RNA Therefore, we conclude that liraglutide can inhibit HCV replication via an AMPK/TORC2-dependent pathway.



Diabetes Ther. 2020 Sep; 11(9): 1909–1914.

ACE2 and SARS-CoV-2 Infection: Might GLP-1 Receptor Agonists Play a Role?

Vincenzo M. Monda, corresponding author1 Francesca Porcellati,2 Felice Strollo,3 and Sandro Gentile4

Key Summary Points

Recently it has been hypothesized that DPP4 inhibitors can have a beneficial effect on SARS-CoV-2 infection through immunoregulating activity.

Experimental study on streptozotocin-treated rats showed that liraglutide was able to stimulate the expression of pulmonary angiotensin converting enzyme 2 (ACE2) and angiotensin (1–7).

Liraglutide modulated different elements of the renin angiotensin system (RAS), significantly increasing ACE2 and Mas receptor (MasR) mRNA expression in pup lungs from food-restricted mothers.

Some action mechanisms support the hypothesis of a protective action of GLP-1R agonists, capable of mitigating a more serious clinical course among SARS-CoV-2-infected individuals with T2DM.



Obes Med. 2021 Jan 6 : 100312.

Friend or foe? ACE2 inhibitors and GLP-1R agonists in COVID-19 treatment

Juan Pang,a,b Mingyao Liu,c Wenhua Ling,a and Tianru Jinb,d,∗


COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a pandemic since WHO made the statement on March 11, 2020. The infection is causing a high mortality in old people, especially those with obesity, type 2 diabetes (T2D) or cardiovascular diseases (CVD). Extra cautions are needed in the treatment of those patients. The CVD drugs ACEIs and ARBs, as well as the T2D drugs GLP-1R agonists, were shown to activate angiotensin-converting enzyme 2 (ACE2) expression in experimental animals. Elevated ACE2 expression may accelerate virus entrance into the host cells during the infection for its replication. However, expression of the soluble ACE2, may neutralize the virus to limit the infection and replication. Given that obese, diabetes and CVD patients often take those medicines in the treatment and prevention of blood pressure and glucose elevation, it remains to be determined whether those medicines represent friend or foe in the treatment of COVID-19. We suggest that retrospective studies should be conducted to determine the exact impact of those medicines in obese, diabetic, or CVD patients who had COVID-19. Results obtained will provide guidance whether those drugs can be utilized in COVID-19 patients with obesity, diabetic, or CVD.